The present invention is directed to compounds useful for treating or preventing one or more disorders, preferably disorders of the central and/or peripheral nervous system. The disorders include depression, psychotic disorders, mood disorders, bipolar disorders, personality disorders, eating disorders, aggressive behavior, schizophrenia, inflammatory bowel disorders, irritable bowel syndrome, pain, chronic neuropathic pain, addiction disorders including cocaine abuse, urinary incontinence, dementia, Alzheimer's memory loss, Parkinsonism, stroke, anxiety, attention-deficit disorder, social phobia, pathological crying and/or laughing, obsessive compulsive disorder, substance (like nicotine, alcohol and opium) abuse and withdrawal (substance related disorder), cognitive disorders, fibromyalgia, Interstitial cystitis, Nocturnal enuresis, Ciguatera poisoning, Body dysmorphic disorder, Lichen simplex chronicus, chronic hiccups and sleep disorders. Included among these disorders are disorders related to depression, such as pseudodementia, migraine pain or headache, bulimia, obesity, pre-menstrual syndrome or late luteal phase syndrome, tobacco abuse, smoking, panic disorder, memory loss, dementia of ageing, acquired immunodefeciency syndrome dementia complex, memory dysfunction in ageing, anti-attention deficit hyperactivity disorder (ADHD), chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, narcolepsy, Gilles de la Tourettes disease, presenile dementia, senile dementia, cognition impairment, sexual dysfunctions, disorders of sleep or autism, mutism or trichotillomania.
The pathophysiology of major depression is poorly understood being a multifactorial syndrome. The increase in the number of individuals with some or other form of central and/or peripheral nervous system disorders has resulted in tremendous efforts towards the development of drugs for central and/or peripheral nervous system. Several classes of drugs with a range of binding selectivities have been discovered and used in the treatment of various central and/or peripheral disorders. The activity of earlier drugs was due to their binding to a broad range of neurotransmitter receptors/re-uptake proteins which led to many undesirable side effects along with considerable delay in the onset of relief. These drugs are not able to meet the treatment goals, have variable response in patients and do not have a favorable profile in modulating neurological and/or psychiatric targets (GPCR and/or non-GPCR).
Azabicyclohexane derivatives are extensively known in the prior art particularly for the treatment of central and/or peripheral nervous system disorders. For example The PCT applications WO 2010025890, WO 2010150281, WO 2010013222, WO 2009090548, WO 2009027293, WO 2009141412, WO 2008117229, WO 2008013856, WO 2008153937, WO 2008075162, WO 2008074716, WO 2008029349, WO 2008053131, WO 2008084300, WO 2007135529, WO 2007127421, WO 2007006117, WO 2007138431, WO 2007016155, WO 2007014264, WO 2007007282, WO 2007135527, WO 2006024955, WO 2006054162, WO 2006064304, WO 2006096810, WO 2006106425, WO 2006117754, WO 2006123121, WO 2006032466, WO 2006002133, WO 2005037790, WO 2005037216, WO 2005005399, WO 2005117872, WO 2005005422, WO 2005005420, WO 2005005398, WO 2005087731, WO 2005026121, WO 2004033451, WO 2004004629, WO 2004014363, WO 2004018422, WO 2004056810, WO 2004089364, WO 2004089943, WO 2003035622, WO 2003027083, WO 2002066427, WO 2002034716, WO 200198267, WO 2000039089, WO 9719942, WO 9736906, WO 9736871 and WO 199515327 disclose azabicyclohexane derivatives, some of which are useful for the treatment of central and/or peripheral nervous system disorders. Similarly, the following applications/patents: US 20090075970, US 20090270364, US 20080176860, US 2005075387, US 20040002504, US 20040147760, US 2003232739, US 20030207876, US 2003207876, US 20030207876, U.S. Pat. No. 6,313,312, U.S. Pat. No. 5,968,929, U.S. Pat. No. 5,475,116, U.S. Pat. No. 5,164,402, U.S. Pat. No. 4,435,419, U.S. Pat. No. 4,435,419, U.S. Pat. No. 4,438,130, EP 1980150, EP 0747355, EP 413455, EP 0129991 and JP2009040709, also disclose azabiclyclohexane derivatives.
Although a number of azabicyclohexane derivatives are described in the art there is an ongoing need for the development of effective and safe compounds for treatment of central and/or peripheral nervous system disorders. Depending upon the selection of different types of substituents on the main scaffold “3-azabicyclohexane”, the specificity or affinity for the different neurological and/or psychiatric targets (GPCR and/or non-GPCR) varies. Thus, it would be advantageous to provide further neurological and/or psychiatric target (GPCR and/or non-GPCR) modulators which can become potential drugs for central and/or peripheral nervous system disorders. The compounds of the present invention are structurally different from the known 3-azabicyclohexane derivatives. These may advantageously possess characteristics such as favorable profile towards modulating different neurological and/or psychiatric targets (GPCR and/or non-GPCR), enhanced potency and/or minimum side effects.